Progress and Trends in In Vivo Chelation of Uranium

“…The strong chelators with target metals will have much greater solubility and stability (i.e., stability constant pK) than other reactions with metals in the aqueous phase [200][201][202][203]. This strength can be shown as pK chelators/pK natural ligands.…”

Section: Chemical Extractionmentioning

confidence: 99%

Characterization and remediation of soils contaminated with uranium

Gavrilescu¹,

Pavel²,

Creţescu³

2009

Journal of Hazardous Materials

506

195

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“…Many chelating agents such as 3,4,3-LIHOPO [19,[34][35][36], Tiron [37,38], ethane-1-hydroxy-1,1-bisphosphonate (EHBP) [39][40][41]46], deferiprone (L1) 1,2-dimethyl-3-hydroxypyrid-4-one [42], DTPA [43], CBMIDA [44] and 1,2-diamino cyclohexyl-tetramethylenetetraphosphonate (CTTP) [45] have been examined for the removal of uranium (Table 4). Although DPTA is often said that it can remove uranium from the body, its effectiveness remains unclear…”

Section: The Use Of Chelating Agents For Minimizing Uranium Body Incomentioning

confidence: 99%

Chelating Agents Used for Plutonium and Uranium Removal in Radiation Emergency Medicine

Fukuda¹

2005

CMC

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The prospects of using chelating agents for increasing the excretion of actinides are reviewed. The removal of plutonium by chelating agents is of great importance because plutonium is extremely dangerous and induces cancer due to radiation toxicity. Similarly, uranium is a radionuclide, which causes severe renal dysfunction within a short time period due to chemical toxicity. It may also induce cancers such as leukemia and osteosarcoma in cases of long-term internal radiation exposure. Investigations on chelating agents for the removal of plutonium were initiated in the 1960's and 1970's. Diethylenetriaminepentaacetic acid (DTPA) is recognized as a chelating agent that accelerates the excretion of plutonium in early treatment after an accident. Thereafter, there has long been an interest in finding new chelating agents with radionuclide removal properties for use in therapy, and many chelating agents such as 3,4,3-LIHOPO and CBMIDA have been studied for their ability to remove plutonium and uranium. Recently, the focus has turned to drugs that have been used successfully in the treatment of a variety of other diseases, for example the iron chelating drug deferiprone or 1,2-dimethyl-3-hydroxypyrid-4-one (L1), which is used in thalassaemia and ethane-1-hydroxy-1,1-bisphosphonate (EHBP), which is used in osteoporosis. Within this context, it is important to examine the clinical use of these two drugs as well as the properties of the experimental chelators 3,4,3-LIHOPO and CBMIDA in order to identify possible uses in the treatment of radiation workers contaminated with plutonium and uranium.

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“…or s.c. administration of DTPA. In a paper by G. N. Stradling, et al, the investigators examined a group of phosphorous-containing ligands, e.g., polyphosphonic acids, biophosphonates and phonoalkylphosphinates, and the hydroxypyridone (HOPO) ligand, 3,4,3-L1(1,2-HOPO), for their ability to decorporate uranium (Hengé-Napoli et al, 1998). Their results underscore the necessity of introducing the decorporation agent soon after contamination; the drug’s efficacy decreased significantly as the interval between exposure and treatment increased.…”

Section: Introductionmentioning

confidence: 99%

Desferrithiocin analogue uranium decorporation agents

Bergeron

Wiegand

Singh

2009

International Journal of Radiation Biology

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Purpose Previous systematic structure-activity studies of the desferrithiocin (DFT) platform have allowed the design and synthesis of analogues and derivatives of DFT that retain the exceptional iron-clearing activity of the parent, while eliminating its adverse effects. We hypothesized that a similar approach could be adopted to identify DFT-related analogues that could effectively decorporate uranium. Materials and Methods The decorporation properties of nine DFT-related analogues were determined in a bile duct-cannulated rat model. Diethylenetriaminepentaacetic acid (DTPA) served as a positive control. Selected ligands also underwent multiple and delayed dosing regimens. Uranium excretion in urine and bile or stool was determined by inductively coupled plasma mass spectroscopy (ICP-MS); tissue levels of uranium were also assessed. Results The two best clinical candidates are (S)-4,5-dihydro-2-[2-hydroxy-4-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid [(S)-4'-(HO)-DADFT-PE (9)], with a 57% reduction in kidney uranium levels on oral (p.o.) administration and (S)-4,5-dihydro-2-[2-hydroxy-3-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid [(S)-3'-(HO)-DADFT-PE (10)], with a 62% renal reduction on p.o. administration. The majority of the metal excretion promoted by these analogues is in the bile, thus further reducing kidney actinide exposure. Conclusions While 9 administered p.o. or subcutaneously (s.c.) immediately post-metal is an effective decorporation agent, withholding the dose (s.c.) until 4 h reduced the activity of the compound. Conversion of 9 to its isopropyl ester may circumvent this issue.

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Progress and Trends in In Vivo Chelation of Uranium

Cited by 23 publications

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Characterization and remediation of soils contaminated with uranium

Characterization and remediation of soils contaminated with uranium

Chelating Agents Used for Plutonium and Uranium Removal in Radiation Emergency Medicine

Desferrithiocin analogue uranium decorporation agents

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